Criteria For Sepsis Research Articles

Sepsis

Maternal sepsis is "a life-threatening condition defined as an organ dysfunction caused by an infection during pregnancy, delivery, puerperium, or after an abortion," with the potential to save millions of lives if a proper approximation is made. Undetected or poorly managed maternal infections can lead to sepsis, death, or disability for the mother, and an increased likelihood of early neonatal infection and other adverse outcomes. Physiological, immunologic, and mechanical changes that occur in pregnancy make pregnant women more susceptible to infections than nonpregnant women and may obscure signs and symptoms of infection and sepsis, resulting in a delay in the recognition and treatment of sepsis. Prioritization of the creation and validation of tools that allow the development of clear and standardized diagnostic criteria of maternal sepsis and septic shock, according to the changes inherent to pregnancy, correspond to highly effective strategies to reduce the impact of these conditions on maternal health worldwide. After an adequate diagnostic approach, the next goal is achieving stabilization, trying to stop the progression from sepsis to septic shock, and improving tissue perfusion to limit cell dysfunction. Management protocol implementation during the first hour of treatment will be the most important determinant for the reduction of maternal mortality associated with sepsis and septic shock.

D-Dimer Levels and the Disseminated Intravascular Coagulation Score to Predict Severity and Outcomes in Sepsis or Septic Shock.

Studies investigating the diagnostic and prognostic value of D-dimer levels and the disseminated intravascular coagulation (DIC) score in sepsis or septic shock commonly include preselected subgroups of patients or were published prior to the current sepsis-3 criteria. Therefore, this study investigates the diagnostic and prognostic impact of D-dimer levels and the DIC score in patients with sepsis and septic shock. Consecutive patients with sepsis and septic shock enrolled in the prospective and monocentric "MARSS" registry from 2019 to 2021 were included. First, the diagnostic value of D-dimer levels was compared to the DIC score to discriminate patients with septic shock from patients with sepsis without shock. Thereafter, the prognostic value of D-dimer levels and the DIC score was tested for 30-day all-cause mortality. Statistical analyses included univariable t-tests, Spearman´s correlations, C-statistics, Kaplan-Meier, as well as uni- and multivariable cox regression analyses. One hundred patients were included (n = 63 with sepsis and n = 37 with septic shock). The overall rate of all-cause mortality at 30 days was 51%. With an area under the curve (AUC) of 0.710 and 0.739, both D-dimer level and the DIC score revealed reliable diagnostic accuracy for the discrimination of septic shock. However, D-dimer levels and the DIC scores were shown to have poor to moderate prognostic accuracy (AUC 0.590 - 0.610) with regard to 30-day all-cause mortality. Specifically, very high D-dimer levels (i.e., > 30 mg/L) (HR = 2.648; 95% CI 1.147 - 6.112; p = 0.023) and a DIC scores ≥ 3 (HR = 2.095; 95% CI 1.095 - 4.009; p = 0.0258) were associated with highest risk of 30-day all-cause mortality. Finally, both higher D-dimer levels (HR = 1.032; 95% CI 1.005 - 1.060; p = 0.021) and DIC scores (HR = 1.313; 95% CI 1.106 - 1.559; p = 0.002) were associated with increased risk of 30-day all-cause mortality after multivariable adjustment. Both D-dimer levels and the DIC scores revealed reliable diagnostic accuracy for the discrimination of septic shock, but a poor to moderate prognostic value for the discrimination of 30-day all-cause mortality. Especially very high D-dimer levels (i.e., > 30 mg/L) and a DIC score ≥ 3 were associated with highest risk of 30-day all-cause mortality.

The Neutrophil-to-Lymphocyte-Ratio as Diagnostic and Prognostic Tool in Sepsis and Septic Shock.

Studies investigating the diagnostic and prognostic value of the neutrophil-to-lymphocyte ratio (NLR) in sepsis or septic shock commonly included preselected subgroups of patients or were published prior to the current sepsis-3 criteria. Therefore, this study investigates the diagnostic and prognostic impact of the NLR in patients with sepsis and septic shock. Consecutive patients with sepsis and septic shock from 2019 to 2021 from the prospective "MARSS-registry" were included monocentrically. First, the diagnostic value of the NLR compared to established sepsis scores was tested for septic shock compared to sepsis. Second, the diagnostic value of the NLR with regard to positive blood cultures was tested. Thereafter, the prognostic value of the NLR was tested for 30-day all-cause mortality. Statistical analyses included univariable t-tests, Spearman´s correlations, C-statistics, Kaplan-Meier analyses, Cox proportional regression analyses as well as uni- and multivariate logistic regression models. A total of 104 patients were included, of which 60% were admitted with sepsis and 40% with septic shock. The overall rate of all-cause mortality at 30 days was 56%. With an area under the curve (AUC) of 0.492, the NLR was shown to have a poor diagnostic value with regard to the diagnosis of septic shock compared to sepsis. However, the NLR was shown to be a reliable parameter to discriminate between patients with negative and positive blood cultures when admitted with septic shock (AUC = 0.714). This was still evident after multivariable adjustment (OR = 1.025; 95% CI 1.000 - 1.050; p = 0.048). In contrast, the NLR revealed a poor prognostic accuracy (AUC = 0.507) with regard to 30-day all-cause mortality. Finally, a higher NLR was not associated with an increased risk of 30-day all-cause mortality (log rank p-value = 0.775). The NLR was a reliable diagnostic tool for the identification of patients with blood culture confirmed sepsis. Yet, the NLR was not a reliable parameter to discriminate between patients with sepsis and septic shock nor between 30-day survivors and non-survivors.

Patients with Bacterial Sepsis Are Heterogeneous with Regard to Their Systemic Lipidomic Profiles.

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. In the present study, we investigated the systemic/serum lipidomic profile at the time of hospital admission for patients with bacterial sepsis. The study included 60 patients; 35 patients fulfilled the most recent 2016 Sepsis-3 criteria (referred to as Sepsis-3) whereas the remaining 25 patients had sepsis only according to the previous Sepsis-2 definition and could be classified as having Systemic Inflammatory Response Syndrome (SIRS). A total of 966 lipid metabolites were identified. Patients fulfilling the Sepsis-3 criteria differed from the Sepsis-2 patients with regard to only 15 lipid metabolites, and especially sphingolipids metabolism differed between these patient subsets. A total of only 43 metabolites differed between patients with and without bacteremia, including 12 lysophosphatidylcholines and 18 triacylglycerols (15 C18/C20 fatty acid metabolites decreased and three C14 myristate acid metabolites that were increased in bacteremia). Unsupervised hierarchical clustering analyses based on the identified sphingolipids, phosphatidylcholine and triacylglycerols showed that (i) the majority of Sepsis-3 patients differed from SIRS patients especially with regard to lysophosphatidylcholine levels; (ii) the minority of Sepsis-3 patients that clustered together with the majority of SIRS patients showed lower Sequential Organ Failure Assessment (SOFA) scores than the other Sepsis-3 patients; and (iii) the variation between the patients in the identified/altered sphingolipid and triacylglycerol metabolites further increased the heterogeneity of Sepsis-3 patients with regard to their systemic lipidomic profile at the time of diagnosis. To conclude, patients fulfilling the Sepsis-3 criteria differ with regard to their metabolic profile, and this variation depends on disease severity.

Monocyte distribution width (MDW) as a useful indicator for early screening of sepsis and discriminating false positive blood cultures.

Severe sepsis and septic shock are the leading cause of in-hospital death. As sepsis progresses, expression and activity of endogenous mediators of inflammation change. Early detection of biomarkers can play a role in sepsis screening and in improvement of patient outcomes. Recent studies suggest that increase in monocyte volume may be helpful in early detection of sepsis. Therefore, we evaluated the utility of monocyte distribution width (MDW) for the early assessment of sepsis compared with the blood culture and other inflammatory biomarkers. Medical records of 1,404 patients (aged ≥19 years) who were admitted to the emergency department owing to clinically suspected infectious disease and requested blood cultures from Oct 2019 to Jan 2021 were reviewed. The patients were grouped based on Sepsis-3 criteria. They had undergone other laboratory tests to evaluate their clinical status. MDW was analyzed using DxH900 hematology analyzer (Beckman Coulter, Brea, California, USA). To determine the diagnostic performance of MDW, C-reactive protein (CRP), and procalcitonin (PCT) for sepsis, the area under the curve (AUC) of receiver operating characteristics curves and their sensitivity and specificity were measured. Among 1,404 patients, 520 patients were designated the sepsis group based on Sepsis-3 criteria. In the sepsis group, MDW value was 24.1 (median, IQR 21.6-28.1); AUC values for MDW, CRP, and PCT were 0.67 (95% CI, 0.64-0.69), 0.66 (95% CI, 0.63-0.68), and 0.75 (95% CI, 0.72-0.77), respectively. For diagnosis of the sepsis, the cut-off value of MDW was 21.7 (sensitivity 74% and specificity 54%). Measured values of MDW were higher for the blood culture positive group than that of the blood culture contamination group (P<0.001, 95% CI, -5.9 to -3.0) or blood culture negative group (P<0.001, 95% CI = -5.8 to -4.2). MDW is a new hematological parameter that is simultaneously calculated during complete blood cell counting by Beckman Coulter hematology analyzer. MDW is expected to serve as a useful indicator for early screening of sepsis in conjunction with CRP and PCT. MDW is especially useful for sepsis assessment in patients with a suspected infection. MDW can also assist in discriminating false positive blood cultures.

Evaluation of complete blood count, c-reactive protein, and lactate dehydrogenase in culturable and unculturable bacteremia for early diagnosis of sepsis

Bacteremia is a bacterial infection that enters the bloodstream. This study was designed to investigate if culture methods could detect the bacterial infection of the bloodstream and to assess certain criteria for bacterial sepsis in culturable and non-culturable blood samples from hospitalized patients, like C-reactive protein (CRP), lactate dehydrogenase (LDH), and complete blood count (CBC). A total of 100 blood samples from patients with symptoms of sepsis who resided in the Hilla City hospital were collected as well as 25 samples as a healthy control group without disease or inflammation. Each sample was divided into three containers; 2ml in an EDTA tube for the CBC test, 3ml in a centrifuged tube for the CRP and LDH test, and 3-7ml in brain heart infusion broth for blood culture. The study result showed that 65 (65%) of 100 samples had abnormal tests, whereas only 25 (25%) of 100 were culture positive. There was a statistically significant difference between patients and control regarding all parameters CRP, LDH, white blood cell (WBC), lymphocyte (LYM) and granulocyte (GRA) (P= 0.000). No significant association in studied parameters was observed between culture-positive and culture-negative patients. Significant strong positive correlation was observed between WBC and LDH (r= 0.332) (p= 0.007), LYM and GR) (r= -0.983) (p= 0.000), LYM and CRP (r= 0.257) (p= 0.03), and between GRA and LDH (r= 0.254) (p= 0.04). Therefore, the estimation of WBC, granulocytes, lymphocytes count, CRP and LDH values and blood culture results may help in the early identification of the causative agent of sepsis.

1178: INCIDENCE AND RISK OF MORTALITY IN PATIENTS ON THREE VASOPRESSORS FOR MANAGEMENT OF SEPTIC SHOCK

Introduction: In patients with septic shock, vasopressors are required to maintain hemodynamics while patients receive treatment for the underlying etiology. Two vasopressors, norepinephrine and vasopressin, are recommend by guidelines for the management of septic shock in the intensive care unit (ICU). However, limited data exist evaluating outcomes associated with the need for a third vasopressor, as well as risk factors for mortality for patients requiring three vasopressors. Evaluation of these risk factors may help with prognostication and goals of care discussions. Methods: The MIMIC-IV and eICU-CRD databases were queried for patients who were, 1) admitted to any ICU, 2) administered at least three vasopressors for at least two hours, and 3) identified to have sepsis based on the Sepsis-3 criteria. Data collected included demographics such as age, sex, and race as well as objective data such as serum creatinine, lactate, Richmond Agitation Sedation Scale (RASS) score, and Sequential Organ Function Assessment (SOFA) score. A generalized additional model (GAM) was developed to evaluate risk factors for in-hospital mortality in the MIMIC-IV and validated using the eICU-CRD. Results: A total of 1,347 and 2,100 patients met inclusion criteria from the MIMIC and eICU databases, respectively. Septic shock requiring three or more vasopressors was associated with a 57.6% in-hospital mortality rate. The model developed from the MIMIC-IV identified increased age (OR [95% CI]: 3.5 [2.3-5.3]), serum creatinine (1.6 [1.5-1.6]), lactate (2.6 [2.5-2.6]), and SOFA score (1.8 [1.1-2.9]) as risk factors for mortality with statistical significance. This model found consistent results within the eICU-CRD. Conclusions: This study demonstrates that patients started on three or more vasopressors face an exceptionally high mortality burden while identifying indicators for those at the highest risk of mortality. These findings may inform management including end-of-life discussions. Future studies should evaluate differences in mortality outcomes based on timing and choice of third-line vasopressor.

1242: PEDIATRIC SEPSIS HAS HIGH MORTALITY REGARDLESS OF PATHOGEN IDENTIFICATION

Introduction: Sepsis remains a major cause of morbidity and mortality in critically ill children worldwide. Culture-negative sepsis (CNS) is diagnosed when a patient meets the criteria for sepsis with no causative pathogen identified. The etiology of CNS may be an uncultivable pathogen, treatment with antimicrobials before a culture was drawn, or a non-infectious cause. For adults, CNS is estimated to comprise up to 50% of all ICU admissions for sepsis, but the characteristics of the pediatric population with CNS are poorly understood. Methods: This is a retrospective cohort study of 3 pediatric ICUs within an urban, tertiary children’s hospital. All patients who received piperacillin-tazobactam, the institution’s standard initial broad-spectrum agent, were screened for study inclusion. Patients ≤18 years old who were hospitalized between March 2020 and February 2021 and met the criteria for sepsis defined in the 2020 Pediatric Surviving Sepsis Guidelines were included in the study. Results: Of the 302 patients screened, 61 met the criteria for sepsis. Thirty-two patients (52.5%) had culture-positive sepsis (CPS) and 29 patients (47.5%) had CNS. The median age for CPS was 5 years (interquartile range [IQR] 1-15y) and 3 years (IQR 0.5-15y) for CNS. Both groups had similar numbers of medically complex patients with >3 comorbidities (68.8% for CPS vs 70% for CNS, p=0.98). There was no statistically significant difference in mortality (28.1% CPS vs 17.2% CNS, p=0.32), need for mechanical ventilation (62.5% vs 58.6%, p=0.19), need for vasoactive medication (62.5% vs 55.2%, p=0.41), or median ICU and hospital length of stay (47 vs 27d, p=0.11; 53 vs. 27d, p=0.07) between groups. CPS patients were treated with longer courses of antibiotics (median 10 vs 7d for CNS p=0.03). Conclusions: When compared to CPS, outcomes for patients with CNS were similar though overall rates of mortality in both groups were high compared to previous reports (4-15%). Patients with CNS comprised a considerable proportion of the total number of patients with sepsis. A median ICU length of stay of 27 days for CNS patients represents significant resource utilization for these individual children. Given these findings, further studies are warranted to better understand this population and determine optimal treatment strategies.

1823. Clinical Profile and Antimicrobial Susceptibility of Invasive Extraintestinal Pathogenic Escherichia coli Disease in Hospitalized Adults Aged ≥60 Years

Abstract Background Invasive extraintestinal pathogenic Escherichia coli disease (IED) occurs more frequently with increasing age, and antimicrobial resistance (AMR) can complicate treatment. Yet IED is under-monitored by major disease surveillance systems. In addition, the diagnosis of IED can be challenging due to the diversity of clinical presentations. More research is warranted to better characterize IED. Here we report EXPECT-2 (NCT04117113) results describing the clinical profile of IED and AMR patterns of causative E. coli isolates. Methods EXPECT-2 was a prospective observational study conducted in patients aged ≥60 years with an IED and hospitalized at 8 sites in Europe, North America, and Asia. Data were collected from October 24, 2019 to January 28, 2021. IED was determined by clinical criteria of either systemic inflammatory response syndrome (SIRS) or Sequential Organ Failure Assessment (SOFA), and a positive E. coli culture either from blood (bacteremic IED), or other normally sterile body site samples and/or urine (non-bacteremic IED). Results Overall, 240 IED patients were enrolled (median age, 75 years; females: 51%); 80.4% of IED cases were bacteremic and 19.6% were non-bacteremic. IED was community-acquired in 50.4%, hospital-acquired in 20.0%, and health care–associated in 29.6% of patients. The most common source of IED was urinary tract (62.9%). Fever occurred in 51.5%, tachycardia in 58.6%, tachypnea in 24.3%, and altered mentation in 15.7% of patients. Laboratory markers of a systemic infection were observed in 86.3% of patients, including leukocytosis in 42.7% and leukopenia in 10.9% of patients. SIRS criteria (≥ 2) were met in 65.8% and SOFA criteria (≥ 2) in 60.4% of patients. According to the investigator, 76.5% of patients met criteria for sepsis and 10.6% for septic shock. At 28 days post diagnosis, 14.6% of patients were unrecovered; 12.9% had a complication of kidney dysfunction, and 4.6% had died. Of 238 patients whose E. coli isolates were tested, the AMR rates for ≥ 1 antibiotic were 62.6% in ≥ 1 drug class, 45.9% in ≥ 2 drug classes, and 35.0% in ≥ 3 drug classes. Conclusion In patients aged ≥ 60 years, IED manifested as a severe infection. AMR was frequently observed. The data suggest a need of preventive interventions for IED. Disclosures Joachim Doua, MD, MPH, Janssen: Employee|Janssen: Stocks/Bonds Jeroen Geurtsen, PhD, Janssen: Employee of Janssen Vaccines &amp; Prevention BV Oscar Go, PhD, Janssen: Employee of Janssen Research &amp; Development LLC. Michal Sarnecki, MD, Janssen: Employee|Janssen: Stocks/Bonds Bart Spiessens, PhD, Janssen: Employee Marc Bonten, MD, PhD, Astra-Zeneca: Advisor/Consultant|Janssen: Advisor/Consultant|Merck: Advisor/Consultant|Novartis: Advisor/Consultant Jan Poolman, PhD, Janssen: Janssen Vaccines &amp; Prevention B.V.|Janssen: Stocks/Bonds.

28: BIOMARKER-BASED RISK STRATIFICATION IN PEDIATRIC SEPSIS FROM A LOW-MIDDLE-INCOME COUNTRY

Introduction: Most biomarker studies of sepsis and acute respiratory distress syndrome (ARDS) originate from high-income countries per World Bank classification, whereas mortality risk is higher in low- and middle-income countries. In children, the second iteration of the Pediatric Sepsis Biomarker Risk Model (PERSEVERE-II) has been validated in multiple North American pediatric intensive care units (PICUs) for prognosis, with areas under the receiver operating characteristic (AUROC) curve of > 0.80 for discriminating 28-day mortality. Given differences in epidemiology, we assessed the performance of PERSEVERE-II in septic children from Pakistan, a low-middle income country, as well as the utility of other select biomarkers. Methods: This was a prospective cohort study of children (age < 18 years) from Aga Khan University Hospital (AKUH) meeting modified pediatric Sepsis-3 criteria (pSOFA ≥ 2 and lactate > 2) between 11/2020 and 2/2022. Plasma was collected < 24 hours of PICU admission and biomarkers measured via single- and multiplex ELISAs. The AUROC for PERSEVERE-II to discriminate 28-day mortality was determined. Additional biomarkers were compared between PERSEVERE-II risk strata (low, medium, and high mortality risk), between survivors and non-survivors, and between those with and without ARDS. Projecting 15% mortality, 73 subjects were needed to detect AUROC > 0.80 at α = 0.05 and power = 0.90. Results: We enrolled 86 subjects with 20 (23%) 28-day non-survivors. PERSEVERE-II discriminated mortality with an AUROC of 0.83 (95% CI 0.72 to 0.94). Non-survivors had higher plasma angiopoietin-2 (ANG2), soluble thrombomodulin (sTM), and plasminogen activator inhibitor 1 (PAI1; all rank-sum p < 0.05), with increasing ANG2 across worsening PERSEVERE-II risk strata. Children who met ARDS criteria within 96 hours had elevated soluble receptor for advanced glycation end-products (sRAGE) and surfactant protein D (SPD; both rank-sum p < 0.05). Conclusions: PERSEVERE-II performs well in septic children from AKUH, representing the first validation of PERSEVERE-II in a low-middle income country. ANG2, sTM, and PAI1 were elevated in non-survivors, and sRAGE and SPD elevated in subjects with ARDS, suggesting a biomarker profile comparable to that of adult and pediatric sepsis and ARDS from high income countries.

Characterization of Mortality by Sepsis Source in Patients Admitted to the Surgical Intensive Care Unit

IntroductionThe impact of infectious source on sepsis outcomes for surgical patients is unclear. The objective of this study was to evaluate the association between sepsis sources and cumulative 90-d mortality in patients admitted to the surgical intensive care unit (SICU) with sepsis. MethodsAll patients admitted to the SICU at an academic institution who met sepsis criteria (2014-2019, n = 1296) were retrospectively reviewed. Classification of source was accomplished through a chart review and included respiratory (RT, n = 144), intra-abdominal (IA, n = 859), skin and soft tissue (SST, n = 215), and urologic (UR, n = 78). Demographics, comorbidities, and clinical presentation were compared. Outcomes included 90-d mortality, respiratory and renal failure, length of stay, and discharge disposition. Cox-proportional regression was used to model predictors of mortality; P < 0.05 was significant. ResultsPatients with SST were younger, more likely to be diabetic and obese, but had the lowest total comorbidities. Median admission sequential organ failure assessment scores were highest for IA and STT and lowest in urologic infections. Cumulative 90-d mortality was highest for IA and RT (35% and 33%, respectively) and lowest for SST (20%) and UR (8%) (P < 0.005). Compared to the other categories, UR infections had the lowest SICU length of stay and the highest discharge-to-home (57%, P < 0.0005). Urologic infections remained an independent negative predictor of 90-d mortality (odds ratio 0.14, 95% confidence interval: 0.1-0.4), after controlling for sequential organ failure assessment. ConclusionsUrologic infections remained an independent negative predictor of 90-d mortality when compared to other sources of sepsis. Characterization of sepsis source revealed distinct populations and clinical courses, highlighting the importance of understanding different sepsis phenotypes.

Association between timing and adequacy of antibiotics and adverse outcomes in patients with sepsis and septic shock: A multicentre retrospective cohort study.

To investigate the association between the timing and adequacy of antibiotics administered to patients presenting with culture-positive sepsis and septic shock to the ED and in-hospital mortality and/or intensive care unit (ICU) admission. Multicentre retrospective cohort study of ED presentations at four metropolitan hospitals in Sydney, Australia between January 2017 and November 2019. Encounters for patients aged ≥16 years meeting specified criteria for sepsis or septic shock with antibiotic administration within the first 6 h of presentation were included. Of 7611 encounters included in the study, 2328 (31%) were culture positive, and 2228 (29%) met the criteria for septic shock. In culture-positive sepsis encounters, partial or inadequate antibiotic coverage was associated with higher risk of death or ICU admission (adjusted odds ratio [AOR] 1.50, 95% confidence interval [CI] 1.04-2.06 and 1.95, 95% CI 1.28-2.99, respectively). This effect was not significant in septic shock encounters (AOR 1.10, 95% CI 0.64-1.88) with partial coverage and (AOR 1.63, 95% CI 0.81-3.3) inadequate coverage. Time to antibiotics was not significantly associated with the risk of mortality/ICU admission. This inference remained the same when analysis was restricted to cases with adequate antibiotic coverage. In a large multicentre sample of patients with culture-positive sepsis, inadequacy of antibiotics was associated with higher risk of in-hospital mortality or ICU admission.

Effect of Serum Ferritin on the Prognosis of Patients with Sepsis: Data from the MIMIC-IV Database.

The present study aimed to investigate the prognostic value of serum ferritin in critically ill patients with sepsis by using the MIMIC-IV database. Data were extracted from the MIMIC-IV database. Adult patients who met the sepsis-3 criteria and had the test of ferritin were included. Patients were divided into subgroups according to the initial serum ferritin. The association between initial serum ferritin and in-hospital mortality was performed by using Lowessregression, logistic regression, and ROC analysis. Subgroup analysis was used to search for the interacting factors and verify the robustness of the results. Analysis of the 2,451 patients revealed a positive linear relationship between serum ferritin and in-hospital mortality. Patients with high-ferritin had a higher risk of in-hospital mortality, but no significant association was found in the low-ferritin subgroup compared with those whose ferritin was in the normal reference range. Serum ferritin had moderate predictive power for in-hospital mortality (AUC = 0.651), with an optimal cut-off value of 591.5 ng/ml. Ferritin ≥591.5 ng/ml acted as an independent prognostic predictor of in-hospital mortality, which increased the risk of in-hospital mortality by 119%. Our findings were still robust in subgroup analysis, and acute kidney injury and anemia were considered interactive factors. High-level serum ferritin was an independent prognostic marker for the prediction of mortality in patients with sepsis. Further high-quality research is needed to confirm the relationship between ferritin and the prognosis of septic patients.

Characterization of a proteomic profile associated with organ dysfunction and mortality of sepsis and septic shock.

The search for new biomarkers that allow an early diagnosis in sepsis and predict its evolution has become a necessity in medicine. The objective of this study is to identify, through omics techniques, potential protein biomarkers that are expressed in patients with sepsis and their relationship with organ dysfunction and mortality. Prospective, observational and single-center study that included adult patients (≥ 18 years) who were admitted to a tertiary hospital and who met the criteria for sepsis. A mass spectrometry-based approach was used to analyze the plasma proteins in the enrolled subjects. Subsequently, using recursive feature elimination classification and cross-validation with a vector classifier, an association of these proteins with mortality and organ dysfunction was established. The protein-protein interaction network was analyzed with String software. 141 patients were enrolled in this study. Mass spectrometry identified 177 proteins. Of all of them, and by recursive feature elimination, nine proteins (GPX3, APOB, ORM1, SERPINF1, LYZ, C8A, CD14, APOC3 and C1QC) were associated with organ dysfunction (SOFA > 6) with an accuracy of 0.82 ± 0.06, precision of 0.85 ± 0.093, sensitivity 0.81 ± 0.10, specificity 0.84 ± 0.10 and AUC 0.82 ± 0.06. Twenty-two proteins (CLU, LUM, APOL1, SAA1, CLEBC3B, C8A, ITIH4, KNG1, AGT, C7, SAA2, APOH, HRG, AFM, APOE, APOC1, C1S, SERPINC1, IGFALS, KLKB1, CFB and BTD) were associated with mortality with an accuracy of 0.86 ± 0.05, a precision of 0.91 ± 0.05, a sensitivity of 0.91 ± 0.05, a specificity of 0.72 ± 0.17, and an area under the curve (AUC) of 0.81 ± 0.08 with a confidence interval of 95%. In sepsis there are proteomic patterns associated with organ dysfunction and mortality.

Prediction of short-term mortality in elderly patients with sepsis using immunoglobulin G2: An observational study

BackgroundSepsis is a global healthcare issue and continues to cause high mortality especially in elderly patients. The humoral immune system plays an important role in protecting from microbial contamination. The goal of this study is to investigate the immune status and prognostic evaluation of elderly patients with sepsis. MethodsA single-center, prospective observational study has been conducted, with the endpoint being the 28-day mortality. Patients 65 years and older who met the diagnostic criteria of Sepsis-3 in the Emergency Department of Beijing Chao-Yang Hospital were divided into survivors and non-survivors groups. Levels of immunoglobulin (Ig) A, IgG, IgM and their subclasses as well as clinical indicators were collected upon enrollment, and the results were statistically analyzed. ResultsThis study finally enrolled 106 elderly patients, including 68 survivors and 38 non-survivors. Compared with survivors, IgG2 level and IgG4 level were lower in non-survivors (P<0.05). IgG2 could be regarded as an independent predictor of the 28-day mortality in elderly septic patients. IgG2 had a higher predictive value than other immunoglobulins, lactate, procalcitonin, SOFA score and APACHE II score for mortality in elderly septic patients, and the ratio of IgG2 to IgG had a slightly larger area under the ROC curve compared to IgG2 only (AUC: 0.776 v.s. 0.741). ConclusionIgG subclasses play important roles in the prognosis of elderly septic patients, with IgG2 being the main component. IgG2 was found to outperform other immunoglobulins, lactate, procalcitonin, SOFA score and APACHE II score in terms of predicting the mortality. A complete immunological evaluation is helpful to guide the prognosis and treatment of patients with age-related infection.

Reduced oxygen saturation entropy is associated with poor prognosis in critically ill patients with sepsis.

Recent studies have found that oxygen saturation (SpO2 ) variability analysis has potential for noninvasive assessment of the functional connectivity of cardiorespiratory control systems during hypoxia. Patients with sepsis have suboptimal tissue oxygenation and impaired organ system connectivity. Our objective with this report was to highlight the potential use for SpO2 variability analysis in predicting intensive care survival in patients with sepsis. MIMIC-III clinical data of 164 adults meeting Sepsis-3 criteria and with 30 min of SpO2 and respiratory rate data were analyzed. The complexity of SpO2 signals was measured through various entropy calculations such as sample entropy and multiscale entropy analysis. The sequential organ failure assessment (SOFA) score was calculated to assess the severity of sepsis and multiorgan failure. While the standard deviation of SpO2 signals was comparable in the non-survivor and survivor groups, non-survivors had significantly lower SpO2 entropy than those who survived their ICU stay (0.107 ± 0.084 vs. 0.070 ± 0.083, p< 0.05). According to Cox regression analysis, higher SpO2 entropy was a predictor of survival in patients with sepsis. Multivariate analysis also showed that the prognostic value of SpO2 entropy was independent of other covariates such as age, SOFA score, mean SpO2 , and ventilation status. When SpO2 entropy was combined with mean SpO2 , the composite had a significantly higher performance in prediction of survival. Analysis of SpO2 entropy can predict patient outcome, and when combined with SpO2 mean, can provide improved prognostic information. The prognostic power is on par with the SOFA score. This analysis can easily be incorporated into current ICU practice and has potential for noninvasive assessment of critically ill patients.

Audit of a computerized version of the Manchester triage system and a SIRS-based system for the detection of sepsis at triage in the emergency department

Background and importanceDifferent triage systems can be used to screen for sepsis and are often incorporated into local electronic health records. Often the design and interface of these digitalizations are not audited, possibly leading to deleterious effects on screening test performance.ObjectiveTo audit a digital version of the MTS for detection of sepsis during triage in the ED.DesignA single-center retrospective studySettings and participantsPatients (n=29766) presenting to an ED of a tertiary-care center who received formal triage were included.Outcome measures and analysisCalculated performance measures included sensitivity, specificity, likelihood ratios, and AUC for the detection of sepsis. Errors in the application of the specific sepsis discriminator of the MTS were recorded.Main resultsA total of 189 (0.7%) subjects met the Sepsis-3 criteria, with 47 cases meeting the criteria for septic shock. The MTS had a low sensitivity of 47.6% (95% CI 40.3 to 55.0) for allocating sepsis patients to the correct triage category. However, specificity was high at 99.4% (95% CI 99.3 to 99.5).

Sindroma Kardiorenal

Cardiorenal syndrome (CRS) atau sindroma kardiorenal merupakan suatu kondisi dimana terjadi penyakit ginjal dan penyakit jantung secara bersamaan yang progresifitasnya terjadi dengan cepat. Pada kasus dimana penyakit jantung merupakan penyakit primer, yang terjadi adalah gangguan dinamika kardioavaskular, aktivasi neurohormonal dan faktor inflamasi yang terlibat dalam awal-mulanya perburukan fungsi ginjal dan penyakit ginjal yang progresif.Sepsis adalah “respons sistemik terhadap infeksi yang telah terdokumenetasi atau masih dicurigai dan terjadi disfungsi satu organ”; terdiri dari hipotermia/hipertermia, takikardia, takipnea, infeksi, dan disfungsi organ akhir akibat hipoperfusi. Sepsis yang lebih modern didasari konsep SIRS, sebuah istilah yang mendeskripsikan kompleks imun sebagai respons infeksi dan digunakan untuk menggambarkan ciri klinis yang berkaitan dengan respons tersebut. Penggunaan klinis SIRS menggambarkan kekacauan laju nafas, frekuensi denyut jantung, temperature, dan jumlah leukosit. Jika ada 2 dari 4 kriteria di bawah ini, SIRS bisa ditegakkan: nafas &gt; 20 kali per menit atau PaCo2 &lt;32 mmHg, frekuensi nadi &gt;90 kali per menit, suhu &gt;38o C atau &lt;36o C, dan leukosit &gt;12,000/mm3 atau &lt;4,000/mm3.CRS sepsis adalah disfungsi renal dan kardiak yang terjadi bersamaan dalam sebuah kondisi sistemik primer yang mempengaruhi kedua organ. “Tuntutan iskemik” jantung didasarkan pada alasan meningkatnya kebutuhan oksigen berkaitan dengan respons sepsis (misalnya takikardia, peningkatan curah jantung) yang mengarah kepada cedera iskemik. Disfungsi renal dapat dilihat selama sepsis berat dan merupakan bagian dari gambaran klinis syok septik dan kegagalan multi organ.

Developing a new sepsis screening tool based on lymphocyte count, international normalized ratio and procalcitonin (LIP score)

Exploring an effective sepsis screening tool that can be widely implemented is important for improving the prognosis of sepsis worldwide. This study aimed to develop a new simple screening tool for sepsis (LIP scoring system) that includes the peripheral blood lymphocyte count, international normalized ratio, and procalcitonin level. In a single-center, prospective, observational study, 444 acute sepsis inpatients and 444 nonsepsis inpatients were ultimately included based on the Sepsis-3 and exclusion criteria. The differences in the Lym, INR, PCT level and other clinical biomarkers were compared between the two groups. Univariable and multivariable logistic regression analyses and receiver operating characteristic analysis were used to establish a LIP screening tool for sepsis with a combination of biomarkers. The Kappa and McNemar tests were used to evaluate the differences between the LIP screening results (LIP score ≥ 3) and Sepsis-3 criteria (SOFA score ≥ 2). Logistic regression analysis showed that the lymphocyte count, INR, PCT level, platelets, neutrophil/lymphocyte ratio (NLR) and prothrombin time (PT) were independent risk factors for the development of sepsis. The ROC analysis showed that the lymphocyte count, INR, and PCT level had high area under the ROC curve values (AUROC (95% CI): Lym 0.84 (0.810–0.860), INR 0.921 (0.902–0.938), PCT level 0.928 (0.909–0.944)). The LIP tool had satisfactory screening efficacy for sepsis (sensitivity, 92.8%; specificity, 94.1%), and a LIP score equal to or greater than 3 points had good agreement with Sepsis-3 criteria in the diagnosis of sepsis (Kappa = 0862 in the Kappa test and P = 0.512 in the McNemar test). The LIP tool has satisfactory sensitivity and specificity for sepsis screening, and it can be used for rapid screening of patients with sepsis in outpatient and emergency departments or in economically underdeveloped areas with limited resources.

Role of CD8+ T cell exhaustion in the progression and prognosis of acute respiratory distress syndrome induced by sepsis: a prospective observational study

BackgroundCD8+ T cells are important for protective immunity against intracellular pathogens. Excessive amounts of antigen and/or inflammatory signals often lead to the gradual deterioration of CD8+ T cell function, a state called “exhaustion”. However, the association between CD8+ T cell exhaustion and acute respiratory distress syndrome (ARDS) has not been studied. This study was conducted to elucidate how CD8+ T cells and inhibitory receptors were related to the clinical prognosis of ARDS.MethodsA prospective observational study in an emergency department enrolled patients who were diagnosed with sepsis-associated ARDS according to the sepsis-3 criteria and Berlin definition. Peripheral blood samples were collected within 24 h post recruitment. CD8+ T cell count, proliferation ratio, cytokine secretion, and the expression of coinhibitory receptors were assayed.ResultsSixty-two patients with ARDS met the inclusion criteria. CD8+ T cell counts and proliferation rates were dramatically decreased in non-surviving ARDS patients. Increasing programmed cell death 1 (PD-1) expression on the CD8+ T cell surface was seen in patients with worse organ function, while an increasing level of T cell immunoglobulin mucin-3 (Tim-3) was associated with a longer duration of the shock. Kaplan–Meier analysis showed that low CD8+ T cell percentages and increased inhibitory molecule expression were significantly associated with a worse survival rate.ConclusionsCD8+ T cells and coinhibitory receptors are promising independent prognostic markers of sepsis-induced ARDS, and increased CD8+ T cell exhaustion is significantly correlated with poor prognosis.